1921
Volume 68, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

A nucleic acid vaccine for dengue-2 virus was developed, consisting of a plasmid DNA vector with the pre-membrane (prM) and envelope (E) genes expressed from a cytomegalovirus promoter. The DNA was adsorbed onto gold microspheres for administration by a gene gun. Expression was demonstrated by transfection of mouse cells in culture where the prM and E antigens were detected intracellularly, and the E antigen was detected in the culture supernatant fluid, similar to a natural infection. The vaccine elicited neutralizing antibodies to dengue-2 virus and antigen-specific cytotoxic T lymphocyte responses in mice. Several vaccination regimens were evaluated in rhesus macaques for the ability to elicit neutralizing antibodies and protect against viremia after challenge with live dengue-2 virus. Neutralizing antibodies were measured in three of three animals that received four 2-μg doses of DNA and in two of six animals that received two 1-μg doses. No antibodies were detected in three animals that received a single 1-μg dose. When dengue virus challenge was performed one month after vaccination, the three animals that received four 2-μg doses exhibited 0, 0, and 1 day of viremia compared with unimmunized controls which exhibited 4, 4, and 6 days of viremia. Three animals that received two 1-μg doses also exhibited 0, 0, and 1 day of viremia, whereas three animals that received a single 1-μg dose exhibited 2, 3, and 5 days of viremia compared with unimmunized controls, which exhibited 4 days of viremia each. When challenge was performed 7 months after vaccination, three animals that received two 1-μg doses exhibited 0, 3, and 5 days of viremia compared with unimmunized controls, which exhibited 4, 5, and 9 days of viremia. These results suggest that a regimen consisting of two 1-μg doses of DNA can confer satisfactory protection at one month, but not at seven months, after vaccination. Long-term protection following DNA vaccination may require revaccination, higher doses of DNA, or a vaccine that contains additional epitopes or adjuvants.

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2003-04-01
2017-09-21
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  • Received : 07 Sep 2002
  • Accepted : 04 Dec 2002

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